Cerebral aneurysm rupture is a leading cause of hemorrhagic strokes. Because unruptured cerebral aneurysms are being more frequently detected and the prognosis of subarachnoid hemorrhage is still poor, clinicians are often required to judge which aneurysms are prone to progression and rupture. Unfortunately our understanding of the natural history of cerebral aneurysms is limited because the processes of aneurysm initiation, growth and rupture are not well understood. Previous studies have identified the major factors involved in these processes: a) arterial hemodynamics, b) wall biomechanics and mechanobiology, and c) peri-aneurysmal environment (PAE). However, little is known about the relative importance of these factors, their interaction in an individual subject, or their variability across at-risk populations. The overall objective of this project is twofold: a) to gain a better understanding of the mechanisms responsible for the progression of cerebral aneurysms, and b) to develop an integrated system for cerebral aneurysm analysis. Our working hypothesis is that the growth pattern of cerebral aneurysms is determined by the distribution of focal wall damage related to exposure to concentrated hemodynamic wall shear stress and the mitigating effect of bone-aneurysm contact. The project will be divided into three basic phases. In Phase I (development), we will develop and integrate aneurysm modeling and characterization tools and database. The hemodynamics modeling suite will be validated with patient-specific in vitro models constructed using rapid prototyping technology and measured with particle image velocimetry and laser Doppler velocimetry. In Phase II (knowledge discovery), a series of growing and stable aneurysms will be selected from a unique longitudinal database of computed tomography angiography (CTA) images of unruptured aneurysms existing at UCLA, and modeled in order to identify hemodynamic and PAE characteristics and wall damage markers that best correlate with aneurysm growth. In Phase III (demonstration), we will conduct a prospective study of aneurysm evolution based on longitudinal CTA data of patients with unruptured cerebral aneurysms in order to evaluate the growth predictors identified in Phase II. The Specific Aims of the project are to: 1. Develop a system for cerebral aneurysm characterization 2. Study associations of hemodynamic and PAE characteristics to aneurysm growth 3. Evaluate growth predictors using prospective longitudinal data of unruptured aneurysms If our hypotheses are proven to be correct, and the methodology is successfully implemented, there will be a huge positive impact upon the clinical management of unruptured brain aneurysms. [unreadable] [unreadable] [unreadable]